Comparison of Xenogeneic Encapsulated Islet Transplantation in Nonhuman Primates With and Without Immunosuppression

Previously, we have shown the long-term efficacy and biocompatibility of chitosan-coated alginate capsule in allogeneic islet transplantation with canine models of diabetes. In this study, we compared the efficacy and immune response of chitosan-coated alginate capsule in xenogeneic islet transplantation with non-human primates (NHPs). Porcine islets were encapsulated alginate crosslinked with BaCl₂, followed by suspension in chitosan solution. Encapsulated porcine islets were transplanted intraperitoneally in NHPs with and without immunosuppressants. Anti-αGal IgM and IgG was measured from the day of transplantation. After transplantation of encapsulated porcine islets, hyperglycemia and exogenous insulin requirements were decreased in the NHP recipients. Porcine C-peptide was detected in plasma after transplantation, but decreased with time. Anti-αGal IgM and IgG began to increase a week after transplantation in NHP without immunosuppressants, while they showed little increase in NHP with immunosuppressants. Exogenous insulin began to be administered to the NHP recipients from 3 to 5 days after transplantation regardless of immunosuppressants. However, daily insulin requirement increased earlier in NHP without immunosuppressants than those with immunosuppressants. Retrieved encapsulated porcine islets from showed fibrosis more than 70% in NHP without immunosuppressants, whereas only 5% of retrieved capsules showed fibrosis in NPH with immunosuppressants. In addition, in NPH with immunosuppressants, dithizone positive islets were observed over a month after transplantation. The use of immunosuppressants in xenogeneic encapsulated islet transplantation in NHP may help reduce fibrosis and improve islet function by modulating immune reaction.